Study of T Cells Targeting CD19/BCMA (CART-19/BCMA) for High Risk Multiple Myeloma Followed With Auto-HSCT
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events
研究概览
简要总结
CART therapy has showed good safety and efficacy in treatment of lymphoma and acute lymphoblastic leukemia. Researchers want to see if this helps people with high risk multiple myeloma after auto-HSCT.To test the safety and efficacy of giving targeting CD19 and BCMA T cells in treating high risk multiple myeloma followed with auto-HSCT.
详细描述
Adults ages 18-75 with high risk Multiple Myelomas (R-ISS III stage or with extramedullary infiltration or with del(17p), t(4;14), t(14;16), t(14;20), 1q21+ or disease progression during treatment).
Design:
Participants may be screened with:
Medical history Physical exam Blood and urine tests Heart tests Bone marrow sample Multiple scans and X-rays Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. The rest of the blood is returned through a needle in the other arm.
The cells will be changed in a laboratory. Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the T cells through the IV within 3 days. Maintenance therapy with IMiDs was received after combined CAR T infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Multiple myeloma patients eligible for auto-HSCT.
- •High risk multiple myeloma (R-ISS III stage or with extramedullary infiltration or with del(17p), t(4;14), t(14;16), t(14;20), 1q21+ or disease progression during treatment).
- •Expected survival ≥ 3 months.
- •Creatinine < 2.0 mg/dl.
- •Blood coagulation function: PT and APTT <2x normal.
- •Arterial blood oxygen saturation>92%.
- •ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
- •Karnofsky scores ≥ 60 and ECOG score≤
- •Adequate venous access for apheresis, and no other contraindications for leukapheresis.
- •Patients should not take immunotherapy in three months prior to CART cells infusion.
- •Voluntary informed consent is given.
排除标准
- •Pregnant or lactating women.
- •Uncontrolled active infection.
- •Active hepatitis B or hepatitis C infection.
- •Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- •Previously treatment with any gene therapy products.
- •Any uncontrolled active medical disorder that would preclude participation as outlined.
- •HIV infection.
- •History of myocardial infarction and severe arrhythmia in half a year.
- •Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- •Patients with fever of unknown origin (T>38℃).
研究组 & 干预措施
anti-CD19 and anti-BCMA CAR
Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the anti-CD19 CAR T cells (on d0) and anti-BCMA CAR T cells as split-dose (40% on d1 and 60% on d2)
干预措施: anti-CD19 and anti-BCMA CAR (Biological)
anti-CD19 and anti-BCMA CAR
Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the anti-CD19 CAR T cells (on d0) and anti-BCMA CAR T cells as split-dose (40% on d1 and 60% on d2)
干预措施: Immunomodulatory drugs (Drug)
结局指标
主要结局
Incidence and severity of adverse events
时间窗: Approximately 2 years
Proportion of subjects with adverse events overall and by severity grade
PFS, response
时间窗: every 6 months after first induction
mPFS of all patients. PFS is defined as time from first induction date to first documentation of PD, or death due to any cause, whichever occurs first. Percentage of patients with sCR. Response was graded according to IMWG response criteria.
CAR-T Pharmacokinetics
时间窗: Minimum of 2 years after first induction
Maximum transgene level, Time to peak transgene levelm, persistence
次要结局
- Patients quality of life(within 1 year post CART infusion)
- MRD negative conversion ratio and persistence(every 3 months for first year, then every 6 months)
- lymphocyte subsets analysis(Minimum of 2 years)
- immune mutation(Minimum of 2 years)